Anti-VEGF Tx for Wet AMD Shows Benefit 5 Years Later

Half of patients still had 20/40 vision or better

Patients with neovascular age-related macular degeneration ("wet" AMD) in the landmark CATT trial, comparing the anti-angiogenic drugs bevacizumab (Avastin) and ranibizumab (Lucentis), who were evaluated 5 years after starting treatment showed clear benefits from the therapies, irrespective of their original treatment assignments, researchers said.

But the results also made clear that vision improvements seen initially with anti-angiogenic therapy for wet AMD are not permanent: After the first 2 years, despite continued treatment, visual acuity resumes a downward trajectory, according to the report, published online in Ophthalmology.

And because patients could switch between bevacizumab and ranibizumab as they wished after the randomized, double-blind phase ended at year 2, the 5-year results say little about the relative benefits and harms of the individual drugs, noted the authors, who were led by Maureen Maguire, PhD, of the University of Pennsylvania in Philadelphia.

"These results emphasize both the tremendous advances over the past 15 years in preserving vision for a large proportion of patients as well as the limitations of current treatment," they wrote. Results were also presented Monday at the Association for Research and Vision in Ophthalmology meeting in Seattle.

CATT (Comparison of AMD Treatments Trials) was a head-to-head study funded by the National Eye Institute that randomized wet AMD patients to either ranibizumab -- an approved drug for the condition -- or bevacizumab, another anti-VEGF drug that is approved for oncology indications but is frequently used off-label for wet AMD, in large part because it is substantially cheaper that ranibizumab.

At year 5, participants who returned for a follow-up examination (71% of those participating in the randomized phase) overall showed a mean decline in visual acuity of 3 Snellen letters relative to baseline, and 11 letters worse than at the end of year 2 -- as patients in both treatment arms initially showed marked improvements in visual acuity.

"This decrease in vision was accompanied by expansion of the size of the total neovascular complex comprising neovascularization, scarring, and atrophy and by persistence of fluid on OCT [optical coherence tomography]," Maguire and colleagues wrote.

Nevertheless, the researchers emphasized that these results are far better than would be expected without treatment.

They noted that 50% of CATT follow-up participants had visual acuity of 20/40 or better, whereas only 20% had acuity of 20/200 or worse. In comparison, only 10% of untreated patients in previous natural-history studies had 20/40 vision or better after just 2 years and 45%-75% had vision of 20/200 or worse.

The drug therapy also appeared better than photodynamic therapy: previous studies of the latter have yielded rates of 20/40 vision of better at 2 years of 15%, and rates of 20/200 or worse of 30%-40%, Maguire and colleagues indicated.

However, they also stressed that the CATT follow-up results probably exaggerate the benefits of drug therapy in the general wet-AMD population. Nearly 30% of participants did not come back for the 5-year exam, and this group included those who quit the randomized phase, were too ill to return for examination, had moved too far away, or simply chose not to return.

"Thus, the CATT Follow-up Study results are likely better than would have been observed if 100% of CATT patients had returned," the researchers indicated.

And while many ophthalmologists might have hoped the follow-up results would shed light on whether one drug is better than the other, Maguire and colleagues said that was impossible.

They did identify a few differences. Most notably, patients originally assigned to bevacizumab showed a slightly smaller decline in acuity during follow-up (9 letters versus 11, P=0.008).

But with "most patients changing drugs over time," conclusions about relative efficacy or safety were elusive.

They did, however, feel comfortable in concluding that both drugs appeared to be effective and reasonably safe.

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